The overall objective of this project is to characterize the biophysical properties of human lenses and elucidate the mechanisms involved in the development of lens fluorescence, pigmentation, aging and brown cataracts. We are continuing with our studies on fluorescence in the lens (human and rat) and on fluorescent peptides and fluorescent compounds derived from normal lenses and from brown nuclear cataracts. Particular emphasis is placed on the use of nondestructive, noninvasive spectroscopic methods (fluorescence, phosphorescence, optical absorption and transmission, ESR, and Raman) for comparing and contrasting the properties of young and old normal lenses and cataractous lenses. We are also correlating the results of these investigations with similar studies on specific proteins and fluorescent peptides derived from these lenses in order to compare the whole lens with the sum of its component structural proteins. As an adjunct to our studies on the photobiologic response of the ocular lens we are also involved in elucidating the photosensitizing mechanisms of 8-methoxypsoralen (8MOP). We have demonstrated that it can enter the ocular lens (rat and human) and can bind to lens proteins following exposure to ambient light. We have recently shown that specific photoadducts can be formed between this drug and free tryptophan moieties as well as with tryptophan residues in individual lens proteins exposed to 360 nm radiation. This implies that 8MOP could (on a long-term basis) accelerate and/or enhance to previously noted age-related UV induced changes in the ocular lens and may even have a potential cataractogenic action. The elucidation of the photosensitizing action of psoralen compounds is of particular importance in view of the increased use of this drug in the therapy of psoriasis.